Using a sensitive and specific radioimmunoassay we have developed for the determination of human calcitonin (HCT) in unconcentrated peripheral blood, we propose to study HCT levels in patients with cancer of the breast. Calcitonin is a hypocalcemic, hypophosphatemic polypeptide hormone secreted by C cells of mammalian thyroid. In 1973, we reported finding increased levels in 35% of cancer patients with spontaneous hypercalcemia. During a study of normocalcemic patients with bronchogenic cancer, it became apparent that over 69% of these patients had calcitonin levels above normal. Was this hypercalcitonemia a response to bone resorption and impending hypercalcemia? Could calcitonin be used as a marker in cancer? Coombes et al. confirmed the high incidence of hypercalcitonemia in bronchogenic cancer and, in addition, showed that 100% of the breast cancer patients with skeletal metastases, studied by them, had high values of blood calcitonin which could be augmented by calcium infusion. In our laboratory a preliminary study of 13 women with metastatic breast cancer in the clinic at the Howard University Hospital showed that 69% had elevated HCT levels. (Many of these patients had undergone prior therapy). We intend to correlate HCT levels with the duration of disease, disease-free period, presence and extent of bone metastases, presence of extra-skeletal metastases, effect of therapy and prognosis. Perhaps HCT may prove to be a marker for breast cancer.